Tbilisi State Medical University

Infertility is a growing concern, with metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and polycystic ovarian syndrome (PCOS) being associated with it. Insulin resistance is seen to be the central feature of these conditions which ends up disrupting hormonal balance and also impairs fertility in both men and women. Hence, understanding the connection between new antidiabetic drugs and fertility can open new possibilities for fertility care. This review studies the role of antidiabetic drugs in improving reproductive outcomes by targeting insulin resistance and related metabolic dysfunctions. Metformin which is the most widely used insulin sensitizer has evidence to improve ovulation in women with PCOS and is seen to be enhancing sperm count, motility and hormone levels in diabetic males by reducing oxidative stress and inflammation. GLP-1 (Glucagon-like peptide-1) receptor agonists include liraglutide and exenatide which support weight loss, improve insulin sensitivity and show positive effects on testosterone levels, ovulation and menstrual regularity. Current growing agents like SGLT2 (Sodium-glucose cotransporter-2) inhibitors and DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors are also being studied for their potential reproductive too. During pregnancy, glycemic control is critical where metformin and insulin are relatively well-studied, newer agents show variable placental transfer and safety profiles. Further research is required to create new treatment protocols and guidelines to fully understand their long-term reproductive effects in both sexes. Antidiabetic drugs that improve insulin sensitivity offer promising avenues for addressing infertility associated with metabolic disorders. However, gaps remain regarding their long-term preconceptional and postconceptional reproductive effects, underscoring the need for further targeted research.

Background/Objectives: Research on the association between change from baseline in patient-reported outcomes (PROs) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) exists. This study evaluated the association between post-baseline PROs and OS in patients with advanced NSCLC who received first-line cemiplimab-based therapy. Methods: We evaluated PRO data from two phase III studies (EMPOWER-Lung 1 [NCT03088540] and EMPOWER-Lung 3 [NCT03409614]) using a Cox proportional hazards model. Twelve pre-specified PRO scales from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Lung Cancer 13 module were evaluated. Landmark analyses were conducted at 3, 6, 9, and 12 months. Time-dependent analyses using change from baseline PROs as a time-dependent covariate were conducted to evaluate the association of post-baseline PRO improvement with OS. Results: At the 3-month landmark, we observed a 56% reduction in the risk of death (HR = 0.44; 95% CI: 0.32-0.62; nominal p < 0.0001) among stable/improved vs. worsened/unobserved PROs for global health status (GHS)/quality of life (QoL). Results at the 6-, 9-, and 12-month landmarks of GHS/QoL were consistent with those at the 3-month landmark. Time-dependent analyses showed that every 10-point improvement in GHS/QoL was associated with a 31% reduction in the risk of death (HR = 0.69; 95% CI: 0.64-0.75; nominal p < 0.0001). Conclusions: In patients with advanced NSCLC who received first-line cemiplimab-based therapy, improvements in post-baseline PROs are associated with improved OS. These results may inform endpoint selection and interpretation of future clinical trials.

The aim is to evaluate the transannular patch (TAP) repair and valve-sparing repair (VSR) techniques following tetralogy of Fallot (TOF) correction, focusing on post-operative complications and cardiac function. A comprehensive search was performed in PubMed, EMBASE, and Scopus using relevant terms like “Tetralogy of Fallot, right ventricular outflow tract (RVOT), VSR, pulmonary valve replacement, transannular-patch repair”. Results indicated that VSR is favored due to its shorter cardiopulmonary bypass duration, preservation of the pulmonary valve, less demanding surgical requirements, shorter post-operative hospital stays, lower mortality rates, survival of at least 30 years, reduced pulmonary regurgitation, decreased right ventricular dysfunction, and improved physical activity tolerance and neurodevelopment. While TAP alleviates RVOT obstruction (RVOTO), it is associated with long-term pulmonary regurgitation. Both TAP and VSR are effective in managing TOF, but VSR provides better valve function preservation and long-term outcomes.

Diabetes mellitus (DM), both Type 1 (T1DM) and Type 2 (T2DM), remains a global health threat. The causes of T1DM are autoimmune destruction of β cells, whereas T2DM is caused by insulin resistance and β-cell dysfunction. Current treatments manage the disease but do not address the genetic or cellular abnormalities. CRISPR/Cas9 is an extremely potent gene editing tool that can potentially cure diabetes by correcting genetic mutations, controlling gene expression, and regenerating β cells. In the CRISPR systems of T1DM, CRISPR technology has been employed to create immune-evasive β-like cells from iPSCs by editing HLA genes and immune checkpoints. In T2DM, specific disease-causing genes such as TCF7L2, GLUT4, and SLC30A8 have been edited to improve insulin regulation. Further, editing of PPARG and FOXO1 has been found to improve insulin sensitivity and suppress hepatic glucose production. GCK (glucokinase), one of the important regulators of glucose sensing in β-cells, has also been a target to increase insulin secretion and normalise glucose homeostasis. The delivery systems are adeno-associated viruses, lipid nanoparticles, and electroporation, among others. Novel tools like Cpf1 improve editing efficiency, particularly in non-dividing cells. Nanocarriers have also improved delivery specificity and reduced degradation. Promising results have been seen with targeting metabolic enzymes like DPP-4 to preclude T2DM dysfunction. However, issues such as off-target effects, immune reactions, mosaicism, limitations in delivery, costs, and ethical viability still remain. Overcoming all these limitations, CRISPR-based approaches have high potential in overcoming treatment control for symptoms and offering long-term, possibly curative, diabetes therapies. Future research is required to refine delivery, enhance safety, and investigate long-term human effects.

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Background: Pediatric toothpastes commonly combine therapeutic fluoride with non-therapeutic additives (flavors, sweeteners, colors, preservatives, surfactants) to improve child acceptability; however, inappropriate fluoride use and uncertainty about additive safety may influence professional recommendations and parental counseling. Objective: To assess knowledge, perceptions, and self-reported practices regarding fluoride use, fluoride-free alternatives, and non-therapeutic additives in pediatric toothpaste among dental undergraduates and dentists in Pakistan. Methods: A cross-sectional observational survey was conducted from September 2025 to January 2026 using a structured, content-validated online questionnaire distributed via academic/professional networks. Clinical-year undergraduates, house officers, general dentists, and postgraduates/specialists were eligible. Descriptive statistics were reported, and group comparisons between undergraduates and qualified dentists were evaluated using chi-square tests (α=0.05) in IBM SPSS Statistics v26. Results: Of 302 responses, 294 were analyzed; 67.9% were undergraduates and 76.2% were female. Awareness of recommended pediatric fluoride concentration was 77.5% overall and higher among dentists than undergraduates (86.3% vs 73.0; p=0.011). Agreement that fluoride prevents caries (91.7%) and concern about fluorosis with overuse (89.1%) were high and similar between groups. Dentists more often recommended the guideline-preferred smear/rice-grain amount for children &lt;3 years (54.7% vs 42.0; p=0.005). Nearly all participants endorsed flavors as important for compliance (99.7%) and supported stricter regulation of fluoride/additives (95.0%). Conclusion: Pakistani dental professionals strongly endorse fluoride efficacy but show clinically relevant gaps in guideline-concordant dosing and variable fluoride knowledge, supporting targeted education and clearer regulation of pediatric toothpaste formulations

Myasthenia gravis (MG) is a long-lasting autoimmune neuromuscular disorder usually reflected by the presence of autoantibodies against acetylcholine receptors at the neuromuscular junction and characterized by either ocular or generalized disease with possible respiratory crisis. The situation has not changed, as diagnostic difficulties and recurrences are still the main problems despite the improvements in diagnostics and immunosuppression. Moreover, the totality of the evidence is pointing to the fact that MG is a disease that also has non-motor manifestations of important clinical significance. The aim of this narrative review was to summarize the literature on MG which takes the position of a multisystem neuroimmune disease and to clarify the mechanisms of immune dysregulation, neuroinflammation, and gut-immune-brain axis that are the cause of the non-motor symptoms such as fatigue, cognitive impairment, mood disturbances, sleep changes, and autonomic dysfunction. A thorough search in PubMed and Google Scholar using terms connected to MG, non-motor symptoms, gut microbiota, gut-brain axis, neuroinflammation, and immune dysregulation led to the discovery of full-text English studies highlighting both systemic and central mechanisms; a qualitative synthesis of themes was drawn up and focused on microbiome composition, metabolites, cytokines, and the changes in immune cells. Studies were consistent in correlating MG with diminished variety of gut microbes, loss of Firmicutes (including Clostridia/Lachnospiraceae and Faecalibacterium) producing butyrate, and increase in munificent taxa (e.g., Streptococcus and Enterococcus), which was in line with Treg cell (Treg) function being diminished and Th17/Treg balance being shifted. The research involving multi-omics techniques pointed toward the conclusion that dysbiosis was a major reason for the widespread disturbance of SCFAs, and also that it disrupted the pathways of KP and BA through the action of receptors such as AhR and TGR5, which was reflected in the metabolomic profile changes of feces (e.g., of cytosine, xanthine, adenine, and methylmalonic).

Background: Mesial temporal lobe epilepsy (MTLE), often associated with hippocampal sclerosis (HS), is the most common form of drug-resistant focal epilepsy. While anterior temporal lobectomy (ATL) has long been considered the gold standard for achieving seizure freedom, the evolution of neuroimaging and minimally invasive technologies has introduced several alternative surgical and ablative interventions. This review synthesizes current evidence regarding the efficacy, safety, and neuropsychological outcomes of various surgical treatments for MTLE. Methods: PubMed, Google Scholar and Scopus were searched for articles that focus on the surgical treatments that treats mesial temporal epilepsy, using keywords such as “MTLE”, “anterior temporal lobectomy”, “seizures”, “radiosurgery”. Analysis was done from 16 studies, focusing on different treatments and different outcomes. Results: Out of 16 studies, resective surgery, specifically ATL, remains the most effective intervention for seizure control, with seizure-freedom rates ranging from 58% to 89.5%. However, ATL is associated with a higher risk of superior quadrantanopia and verbal memory decline in the dominant hemisphere. SAH approaches, particularly via the subtemporal route, offer comparable seizure control with improved preservation of verbal memory. Minimally invasive LITT demonstrates seizure-freedom rates of approximately 53% to 66.7% while significantly reducing hospital stay and preserving functions. SRS offers a non-invasive alternative but with lower seizure-freedom rates (52%) and a delayed therapeutic effect. Conclusion: The surgical management of MTLE is shifting toward a personalized approach. While open resective surgery provides the highest probability of a seizure-free life, minimally invasive techniques like LITT offer an attractive balance for patients prioritizing cognitive preservation and rapid recovery. Stereotactic radiosurgery and RF-TC remain valuable for specific patient populations where open surgery or thermal ablation is contraindicated.

Schizophrenia is associated with subtle brain structural alterations, but separating disease from medication effects is challenging. Antipsychotic dopamine D2 receptor (D2R) antagonism has been associated with striatal volume increases, but effects of partial D2R agonism by newer antipsychotics are largely unexplored. This study aimed to compare short-term brain changes associated with either D2R antagonism or partial D2R agonism using normative modeling. Secondarily, the study aimed to explore long-term effects following naturalistic treatment. Antipsychotic-naïve patients with first-episode psychosis received 6 weeks of monotherapy with either amisulpride (D2R antagonist) (N = 41) or aripiprazole (partial D2R agonist) (N = 45). All patients underwent structural magnetic resonance imaging before and after 6 weeks of treatment. A subset was re-scanned at 6 months, 1 year, and 2 years of naturalistic treatment. A pretrained normative model was applied to 186 subcortical and cortical regions. We used Wilcoxon signed-rank tests to identify longitudinal structural deviations. Amisulpride and aripiprazole were associated with striatal volume increases after 6 weeks. No cortical effects were observed with amisulpride. Thinning of the temporal lobe was observed with aripiprazole. After 6 months, and 1 and 2 years, the striatal changes abated but cortical thinning in the frontal lobes emerged. Both partial D2R agonism and D2R antagonism appear linked to striatal volume increases; however, changes appear transient. Conversely, frontal thinning occurs over time and appears less closely linked to antipsychotic treatment. Interpreting structural brain changes in patients with psychosis require consideration of short-term pharmacological effects as well as factors related to illness progression.

This article provides perspectives on the use of Cerebrolysin as an adjunct treatment to reperfusion therapy in acute ischemic stroke (AIS). In the evolving landscape of AIS reperfusion therapy, we hypothesize that adjunctive cerebroprotective therapy, such as Cerebrolysin, is likely to further improve patient outcomes. Beyond its established neurorecovery benefits, recent data indicate that Cerebrolysin also offers protection to the neurovascular unit and the blood-brain barrier. This paper introduces the CErebrolysin in RECanalization And Perfusion (CERECAP) program, a collaborative initiative of independent academic investigations exploring the favorable trends of Cerebrolysin in reperfusion. The CERECAP program has generated compelling data demonstrating Cerebrolysin's alignment with current AIS reperfusion therapy concepts, particularly its role in early intervention targeting multiple pathways. We review these studies and discuss the critical need to clearly define the patient population that benefit most from adjunctive Cerebrolysin therapy in AIS.